Bilobalide attenuates lipopolysaccharide‑induced HepG2 cell injury by inhibiting TLR4‑NF‑κB signaling via the PI3K/Akt pathway

Mao,Shumei; Yao,Jinpeng; Zhang,Teng; Zhang,Xiang; Tan,Wei; Li,Chengde

doi:10.3892/etm.2023.12312

Bilobalide attenuates lipopolysaccharide‑induced HepG2 cell injury by inhibiting TLR4‑NF‑κB signaling via the PI3K/Akt pathway

Authors:
- Shumei Mao
- Jinpeng Yao
- Teng Zhang
- Xiang Zhang
- Wei Tan
- Chengde Li
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Affiliations: Department of Pharmacology, Weifang Medical University, Weifang, Shandong 261053, P.R. China, Department of Cardiology, Yantai Kaifaqu Hospital, Yantai, Shandong 264006, P.R. China, Department of Respiratory Medicine, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Clinical Pharmacy, Key Laboratory of Applied Pharmacology in Universities of Shandong, Weifang Medical University, Weifang, Shandong 261053, P.R. China
Published online on: November 22, 2023 https://doi.org/10.3892/etm.2023.12312
Article Number: 24
Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammation is involved in the pathological process underlying a number of liver diseases. Bilobalide (BB) is a natural compound from Ginkgo biloba leaves that was recently demonstrated to exert hepatoprotective effects by inhibiting oxidative stress in the liver cancer cell line HepG2. The anti‑inflammatory activity of BB has been reported in recent studies. The major objective of the present study was to investigate whether BB could attenuate inflammation‑associated cell damage. HepG2 cells were cultured with lipopolysaccharide (LPS) and BB, and cell damage was evaluated by measuring cell viability using MTT assay. The activity of the NF‑κB signaling pathway was assessed by measuring the levels of IκBα, NF‑κB p65, phosphorylated (p)‑IκBα, p‑p65, p65 DNA‑binding activity and inflammatory cytokines IL‑1β, IL‑6 and TNF‑α. A toll‑like receptor (TLR)4 inhibitor (CLI‑095) was used to detect the involvement of TLR4 in cell injury caused by LPS. In addition, the PI3K/Akt inhibitor LY294002 was applied to explore the involvement of the PI3K/Akt axis in mediating the effects of BB. The results demonstrated that LPS induced HepG2 cell injury. LPS also elevated the levels of p‑IκBα, p‑p65, p65 DNA‑binding activity and inflammatory cytokines. However, CLI‑095 significantly attenuated the LPS‑induced cell damage and inhibited the activation of NF‑κB signaling. BB also dose‑dependently attenuated the LPS‑induced cell damage, activation of NF‑κB signaling and TLR4 overexpression. Furthermore, it was observed that LY294002 diminished the cytoprotective effects of BB on cell injury, TLR4 expression and NF‑κB activation. These findings indicated that BB could attenuate LPS‑induced inflammatory injury to HepG2 cells by regulating TLR4‑NF‑κB signaling.

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